Digital Commons Network^™

Phase I Study Of Anti-Epidermal Growth Factor Receptor Antibody-Drug Conjugate Serclutamab Talirine: Safety, Pharmacokinetics, And Antitumor Activity In Advanced Glioblastoma, Benedito A Carneiro, Saiama N Waqar, Et Al.

2020-Current year OA Pubs

BACKGROUND: Serclutamab talirine (Ser-T, formerly ABBV-321) is an antibody-drug conjugate consisting of an antibody (AM-1-ABT-806) directed against activated epidermal growth factor receptor (EGFR) and a pyrrolobenzodiazepine dimer. We investigated Ser-T monotherapy in a phase I, first-in-human, dose-escalation, and dose-expansion study in patients with advanced solid tumors associated with EGFR overexpression.

METHODS: Eligible patients (≥18 years) had advanced, histologically confirmed solid tumors associated with EGFR overexpression (centralized testing). Patients received Ser-T intravenously once every 4 weeks (Q4W; 5-50 μg/kg) in the dose-escalation phase. Herein, preliminary antitumor activity at the recommended phase II dose (RP2D) is reported only for patients with glioblastoma …

Nonalcoholic Fatty Liver Disease Is A Risk Factor For Thiopurine Hepatotoxicity In Crohn's Disease, Alvin T George, Matthew Glover, Quazim Alayo, Maria Zulfiqar, Daniel R Ludwig, Matthew A Ciorba, Scott Mchenry, Parakkal Deepak

2020-Current year OA Pubs

BACKGROUND: Patients with Crohn's disease (CD) are predisposed to nonalcoholic fatty liver disease (NAFLD). CD management often includes thiopurines which can promote hepatotoxicity. We aimed to identify the role of NAFLD on the risk of developing liver injury from thiopurines in CD.

METHODS: In this prospective cohort analysis, CD patients at a single center were recruited 6/2017-5/2018. Patients with alternative liver diseases were excluded. The primary outcome was time to elevation of liver enzymes. Patients underwent MRI with assessment of proton density fat fraction (PDFF) on enrollment, where NAFLD was defined as PDFF >5.5%. Statistical analysis was performed using a …

Perspectives 2023, Oberlin College Libraries

Perspectives Annual Reports

No abstract provided.

Autologous T Cell Therapy For Mage-A4+ Solid Cancers In Hla-A*02+ Patients: A Phase 1 Trial, David S Hong, Brian A Van Tine, Armin Ghobadi, Amanda Cashen, Et Al.

2020-Current year OA Pubs

Affinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancer/testis antigen expressed at varying levels in multiple solid tumors. We conducted a multicenter, dose-escalation, phase 1 trial in patients with relapsed/refractory metastatic solid tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head and neck cancer ( NCT03132922 ). The primary endpoint was safety, and the secondary efficacy endpoints included overall response rate (ORR) and duration of response. All patients (N = 38, nine tumor types) experienced …

Sik3 And Wnk Converge On Fray To Regulate Glial K+ Buffering And Seizure Susceptibility, Lorenzo Lones, Aaron Diantonio

2020-Current year OA Pubs

Glial cells play a critical role in maintaining homeostatic ion concentration gradients. Salt-inducible kinase 3 (SIK3) regulates a gene expression program that controls K+ buffering in glia, and upregulation of this pathway suppresses seizure behavior in the eag, Shaker hyperexcitability mutant. Here we show that boosting the glial SIK3 K+ buffering pathway suppresses seizures in three additional molecularly diverse hyperexcitable mutants, highlighting the therapeutic potential of upregulating glial K+ buffering. We then explore additional mechanisms regulating glial K+ buffering. Fray, a transcriptional target of the SIK3 K+ buffering program, is a kinase that promotes K+ uptake by activating the Na+/K+/Cl- …

Multi-Omic Association Study Identifies Dna Methylation-Mediated Genotype And Smoking Exposure Effects On Lung Function In Children Living In Urban Settings, Matthew Dapas, Michelle A. Gill, Et Al

2020-Current year OA Pubs

Impaired lung function in early life is associated with the subsequent development of chronic respiratory disease. Most genetic associations with lung function have been identified in adults of European descent and therefore may not represent those most relevant to pediatric populations and populations of different ancestries. In this study, we performed genome-wide association analyses of lung function in a multiethnic cohort of children (n = 1,035) living in low-income urban neighborhoods. We identified one novel locus at the TDRD9 gene in chromosome 14q32.33 associated with percent predicted forced expiratory volume in one second (FEV1) (p = 2.4x10-9; βz = -0.31, …

The Mutational Landscape In Chronic Myelomonocytic Leukemia And Its Impact On Allogeneic Hematopoietic Cell Transplantation Outcomes: A Center For Blood And Marrow Transplantation Research (Cibmtr) Analysis, Matthew Mei, Ravi Vij, Et Al.

2020-Current year OA Pubs

Somatic mutations are recognized as an important prognostic factor in chronic myelomonocytic leukemia (CMML). However, limited data are available regarding their impact on outcomes after allogeneic hematopoietic cell transplantation (HCT). In this registry analysis conducted in collaboration with the Center for International Blood and Marrow Transplantation Registry database/sample repository, we identified 313 adult patients with CMML (median age: 64 years, range, 28- 77) who underwent allogeneic HCT during 2001-2017 and had an available biospecimen in the form of a peripheral blood sample obtained prior to the start of conditioning. In multivariate analysis, a CMML-specific prognostic scoring system (CPSS) score of …

Efficacy Of Laser Interstitial Thermal Therapy For Biopsy-Proven Radiation Necrosis In Radiographically Recurrent Brain Metastases, Michael Chan, Albert H Kim, Eric Leuthardt, Et Al.

2020-Current year OA Pubs

BACKGROUND: Laser interstitial thermal therapy (LITT) in the setting of post-SRS radiation necrosis (RN) for patients with brain metastases has growing evidence for efficacy. However, questions remain regarding hospitalization, local control, symptom control, and concurrent use of therapies.

METHODS: Demographics, intraprocedural data, safety, Karnofsky performance status (KPS), and survival data were prospectively collected and then analyzed on patients who consented between 2016-2020 and who were undergoing LITT for biopsy-proven RN at one of 14 US centers. Data were monitored for accuracy. Statistical analysis included individual variable summaries, multivariable Fine and Gray analysis, and Kaplan-Meier estimated survival.

RESULTS: Ninety patients met …

Functional Divergence Of The Sarcomeric Myosin, Myh7b, Supports Species-Specific Biological Roles, Lindsey A. Lee, Samantha K. Barrick, Artur Meller, Jonathan Walklate, Jeffrey M. Lotthammer, Jian Wei Tay, W. Tom Stump, Gregory Bowman, Michael A. Geeves, Michael J. Greenberg, Leslie A Leinwand

2020-Current year OA Pubs

Myosin heavy chain 7b (MYH7b) is an evolutionarily ancient member of the sarcomeric myosin family, which typically supports striated muscle function. However, in mammals, alternative splicing prevents MYH7b protein production in cardiac and most skeletal muscles and limits expression to a subset of specialized muscles and certain nonmuscle environments. In contrast, MYH7b protein is abundant in python cardiac and skeletal muscles. Although the MYH7b expression pattern diverges in mammals versus reptiles, MYH7b shares high sequence identity across species. So, it remains unclear how mammalian MYH7b function may differ from that of other sarcomeric myosins and whether human and python MYH7b …

Discerning Friend From Foe: Systematic Revision Of Cuscuta L. Section Indecorae Using A Combined Ecological, Morphometric, And Phylogenetic Approach., Corey Burt

Theses and Dissertations (Comprehensive)

The genus Cuscuta (Dodder; Convolvulaceae) are obligate parasitic plants. In one clade known as section Indecorae, there are species which are considered pests that pose significant threats to agricultural crop production, while other species are rare or known only from historical records. Section Indecorae contains three species: C. coryli, C. warneri, and C. indecora (the latter with three infraspecific taxa: var. indecora, var. longisepala, and var. attenuata). The systematics of section Indecorae are not currently resolved. Cuscuta indecora has a long and complicated taxonomic history with many infraspecific varieties described, and …

I Am Queer And Asian: The Crossroad Of Race And Lgbtqia+ Identity Among Queer Asian Canadian Youth And The Impacts Of The Covid-19 Pandemic, Kenny Chee

Theses and Dissertations (Comprehensive)

LGBTQIA+ Asian youth face unique challenges due to their intersecting identities. Utilizing Asian Critical Race Theory and the Integration Model of Stress and Trauma in LGBTQIA+ Asians, LGBTQIA+ Asian youth are likely to experience detrimental mental health outcomes due to the stigmatization within their Asian culture and racial discrimination from the LGBTQIA+ communities. Moreover, the COVID-19 pandemic exacerbated existing challenges because of the closure of community spaces and increased hate crimes against Asians. Nonetheless, research on the intersectional experiences of LGBTQIA+ Asians in Canada, especially in the context of the COVID-19 pandemic is sparse. Thus, to address this gap, I …

Temperature Regulation Of Pipecolic Acid-Mediated Plant Systemic Immunity In Arabidopsis Thaliana, Alyssa Shields

Theses and Dissertations (Comprehensive)

Significant crop losses are caused by pathogenic infections annually, which are exacerbated by increasing global temperatures due to climate change. One way by which plants respond to pathogenic attacks is through the activation of pattern-triggered immunity (PTI), effector-triggered immunity (ETI), and systemic acquired resistance (SAR), which lead to production of the central defence phytohormone salicylic acid (SA). Accompanying SA release is the putative mobilization of pipecolic acid (Pip), which acts as an immune regulatory plant metabolite that works with and independently from SA. As demonstrated in the model plant Arabidopsis thaliana following infection with the model bacterial pathogen Pseudomonas syringae …

Wildlife Value Orientations And Recreation Conflict: A Focus On Hunters And Non-Hunters In Alberta, Canada, Yuvana Sequeira

Theses and Dissertations (Comprehensive)

Parks and other forms of protected areas are considered a vital tool in the effective conservation of biodiversity. These areas also provide important spaces for nature-based tourism and recreation (NBTR), where activities such as hiking, swimming, canoeing, and socializing with friends and family often occur. In some cases, hunting may also occur within a protected area, but there is little understanding of how such activities affect the experience and overall satisfaction of other recreationists (and vise-versa). While NBTR is a popular and growing industry, there is limited research in Canada about the values of tourists and recreationists and the …

Examining Foot And Lower Leg Muscular Activation During Slip Recovery, Keara Sutherland

Theses and Dissertations (Comprehensive)

Slips during gait are the leading cause of falls and subsequent serious injury in young and older adults. Reactive balance responses generated by the lower limb muscles can restore balance and minimize the chance of experiencing a fall. The purpose of this study was to examine the role of the deep muscles in the lower leg and muscles within the foot during recovery from an unexpected slip perturbation. We hypothesized that lower leg musculature and intrinsic foot muscles would exhibit an earlier onset, longer duration, and increased magnitude during slips compared to level walking and that muscle activity would have …

Characterization Of The Clostridioides Difficile Glycosyl Hydrolase Ccsz, Brian Lowrance

Theses and Dissertations (Comprehensive)

Bacteria inhabit many of the harshest environments on Earth; persisting and thriving in conditions thought to be unsuitable for life. One common strategy to withstand these environments is the formation of a biofilm. Biofilm composition varies greatly, depending on the underlying community that produces it. Cellulose, a polymer consistently prevalent in biofilms, has been identified as a virulence factor in many pathogens and is suspected to be involved in pathogenesis by Clostridioides difficile. C. difficile is the #1 cause of hospital acquired diarrhea, which can range from mild to life-threatening infections. Biofilm formation is hypothesized to be involved in …

Employees’ Reactions To Their Supervisors’ (Lack Of) Discretionary Adjustments In Performance Evaluations, Joanna Andrejkow

Theses and Dissertations (Comprehensive)

The purpose of my dissertation is to investigate how employees react to their supervisors’ decisions not to use ex-post discretionary adjustments to mitigate the effects that negative unexpected events have on their bonuses. To address this objective, I pose the following research question: Will the level of interdependence inherent within the compensation of multiple employees (i.e., compensation interdependence) and the likelihood the event will reoccur (i.e., future event likelihood) affect employees’ reactions (future effort and workplace deviance) when they don’t receive ex-post discretionary adjustments to mitigate the effects of negative events?

I address my research question using an experiment where …

Disrupting And Expanding The Discourse: Palliative Care Clinicians' Experiences With Patients' Non-Physical Suffering, Maxxine Rattner

Theses and Dissertations (Comprehensive)

While one of the primary aims of palliative care is to prevent and relieve suffering, both physical and non-physical, research to date has been very limited re: clinicians’ experiences with patients’ non-physical suffering (e.g., suffering that may be psychological, emotional, social, spiritual and/or existential in nature); both how clinicians work with/respond to this kind of suffering in their day-to-day work, and the effect of this aspect of their work on clinicians themselves. No research to date has considered the impact of palliative care’s dominant non-physical suffering discourse — which presents the relief of non-physical suffering as falling along a binary …

Vapourized Cannabis Extract Administration Impairs Memory And Alters Neural Activity In Laboratory Rats, Megan Chladny

Theses and Dissertations (Comprehensive)

Although people have smoked cannabis for millennia, administration of cannabis by heating the dried plant material or distilled extracts to a temperature just below the combustion point (i.e., vapourization or "vaping") has rapidly increased over the past few years (Javadi-Payder, Cole, and Taffe, 2018; Manwell, Charchoglyan, Brewer, Matthews, Heipel, and Mallet, 2014). Conversely, most of the cannabinoid research using rodent models has used parenteral routes of administration to examine the effects of purified cannabis extracts such as ∆⁹-tetrahydrocannabinol (THC), making it difficult to directly compare laboratory research to human drug use. Building on previous studies showing that THC …

Assessing The Biocatalytic Promiscuity Of Pep- Transformations For Geminal-Difluorination, Eloy Jose Torres Garcia

Theses and Dissertations (Comprehensive)

Fluorine is the most electronegative chemical element and can drastically change molecular properties, such as drug pharmacokinetics and agrochemical half-life. Although a great deal of progress is occurring in synthetic methods to access various organofluorines, these methods struggle with harsh conditions and limited substrate scope. Biocatalytic approaches offer the potential to access organofluorines that are difficult or impossible with the current methodology. Phosphoenolpyruvate (PEP) is a central metabolite and biosynthetic precursor for diverse molecules. Phosphoenol pyruvate mutase (Ppm) catalyses the interconversion of Phosphonopyruvate (PnPy) to Phosphoenolpyruvate (PEP). This research successfully expressed and …

Investigating The Effects Of Disturbance And Competition On Establishment, Growth, And Reproduction Of The Endangered Ripariosida Hermaphrodita, Daniel Engelking

Theses and Dissertations (Comprehensive)

Ripariosida hermaphrodita (Virginia Mallow) is a perennial riparian plant with broad, maple-like leaves. It grows up to three meters high and is often found in large clonal patches, but sexually reproduces readily. While this plant may seem like a redoubtable competitor when growing in large colonies, it is declining across its range in North America. The only known occurrences in Canada are in southern Ontario. Prior to this study, no new populations had been recorded even though one of the known populations produces copious amounts of viable seed with potential to disperse. There are many hypotheses for its rarity, but …

Distinctiveness And Similarity: How The Sub-Trait Facets Of The Big Five Self-Organize To Create Personality Types, Jonathan Thiessen

Theses and Dissertations (Comprehensive)

The belief that people can be placed within a personality typology has persisted for millennia. At least as far back as Hippocrates (ca. 460 BCE–370 BCE) people were believed to be of a kind based on the four humors—blood, yellow bile, black bile, and phlegm. Since then, there have been many conceptions of personality typologies. The Myers-Briggs Type Indicator and the Enneagram of Personality are likely the most well-known personality typologies among the general public. Despite their wide public usage, neither typology boasts strong empirical support. However, psychology continues to investigate personality for evidence of a typology of personality. In …

Differences In Drifting Invertebrate Communities Across Arctic Ecozones And The Influence On Potential Growth Of Grayling (Thymallus Arcticus), Charles Chanyi

Theses and Dissertations (Comprehensive)

Invertebrate drift is a key process that potentially affects multiple levels of food web organization within stream environments. However, our understanding of the mechanistic drivers of drift in high latitude streams and subsequent bottom-up control that drift may have on fish predators in these environments remains understudied. This project aimed to gain the baseline knowledge of how drift functions across two major high latitude ecozones, the boreal forest and tundra, and how those possible differences in drifting community characteristics may impact drift-feeding Arctic grayling (Thymallus arcticus). These objectives were accomplished by characterizing stream environments across both ecozones, sampling …

Examining The Effects Of Noise And Task Dependent Performance In Prosody Perception In Autistic Individuals, Zehranur Sasal

Theses and Dissertations (Comprehensive)

ABSTRACT

Objective: It is known that autistic individuals have enhanced abilities in pitch discrimination and tend to excel in low-level tasks requiring lower cognitive processing. On the other hand, noise is a distracting factor in many areas of life, including prosody perception. The studies presented in this thesis aimed to understand prosody perception through different levels of cognitive tasks and under the influence of speech background noise.

Methods: In total, 256 non-autistic and 39 high-functioning autistic adults participated in these studies. In the first study, participants were asked to listen to brief utterances conveying one of six universally accepted emotions …

The Design And Characterization Of Gold Nanoclusters As Elementary Building Blocks, Heather Gaebler

Theses and Dissertations (Comprehensive)

Gold nanoclusters with diameters in the quantum size regime (< ~2 nm) are promising building blocks for the design of novel nanomaterials as they exhibit unique size-dependent properties that can be altered and fine-tuned. The research outlined in this PhD thesis employs density functional theory to construct and analyze small ligand-protected cage and rod-shaped nanoclusters. Chapter 2 reports stable halide-protected gold nanocages that were engineered to have a closed-shell valence electron count of 18. This study finds that nanocages comprised of 19 and 20 gold atoms can be converted into stable magic number species containing 18 valence electrons by modifying their charged states via adsorption of halide ligands to the cage’s surface. Chapter 3 reports stable ligand-protected gold nanoclusters with a tetrahedral Au₄ core that were engineered to have a closed-shell valence electron count of 2. This study investigates the structural and electronic effects of halide and alkoxy ligands on the tetrahedral nanocluster and concludes that the results support the broader conclusion that it’s possible to fine-tune the stability and electronic properties of small gold nanoclusters using appropriate ligands. Chapter 4 reports stable gold nanorods that have diameters in the quantum regime that were constructed from elementary building blocks that contain “halide-staples”. This study presents different orientations of the “halide-staple” motifs on …

Exploring The Effectiveness Of Ecological Momentary Assessment And Video At Eliciting The Impact Of Park Features On Human Health And Well-Being In A Protected Area Context, Katelyn O'Bright

Theses and Dissertations (Comprehensive)

It is increasingly recognized that contact with nature in parks and other forms of protected areas provides benefits to visitors’ physical, mental, social, spiritual, and intellectual health and well-being. However, the methods used to assess these outcomes, including the influence of different environmental features that lead to these benefits, is under-researched. To address this gap, this study used a mixed methods design to explore the effectiveness of using Ecological Momentary Assessment (EMA) and video to assess the impact of various park features on the self-perceived (subjective) health and well-being of visitors. Participants were prompted by a mobile application on their …

Temperature Regulation Of Plant- Rhizobacteria Interactions Within The Soil-Rhizosphere- Rhizoplane Interface, Eric J. R. Marchetta

Theses and Dissertations (Comprehensive)

An optimal microbiome is important for plant health and can prime subsequent plant immune responses to enhance stress resilience. However, the molecular mechanisms that dynamically drive host-microbiome interactions and subsequent induced systemic resistance (ISR) responses in plants under elevated environmental temperatures remain underexplored. To address this major knowledge gap, this thesis further investigated Canadian soil-inhabiting rhizobacteria that had been previously shown to activate ISR in tomato (Solanum lycopersicum) plants. Specifically, this study characterized the in vitro physiology of these rhizobacterial strains under different temperatures, including growth, phosphate solubilization abilities and direct anti- pathogenic capabilities. Temperature-sensitivity of these parameters …

Natural Variation In Temperature-Modulated Immunity To Pseudomonas Syringae Pv. Tomato (Pst Dc3000) In Arabidopsis Thaliana Plants, Christina A. M. Rossi

Theses and Dissertations (Comprehensive)

Studies conducted on the model plant-pathogen system Arabidopsis thaliana-Pseudomonas syringae pv. tomato (Pst) showed that elevated temperature suppresses the pathogen-induced production of salicylic acid (SA), which is a key plant defence hormone. This increased host vulnerability at higher temperatures is due to downregulated expression of CALMODULIN BINDING PROTEIN 60-LIKE G (CBP60g) and SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1 (SARD1), which encode master regulators of SA production. Collectively, these previous studies only focused on one natural accession of Arabidopsis called Columbia-0 (Col-0). However, the intraspecific variation in Arabidopsis immunity phenotypes under elevated temperature remains unknown. To fill this critical knowledge gap, my …

Optimization Of The Modular Reinforced Bone Scaffold For Customized Alveolar Bone Defects, Meisam Omidi, Luis Eduardo Almeida, Lobat Tayebi

School of Dentistry Faculty Research and Publications

A modular reinforced bone scaffold with enhanced mechanical properties has recently been developed by our group. It includes: 1) A load-bearing module: a skeleton which is made of a slowly degradable material, undertaking mechanical necessities of the scaffold, and 2) A bio-reactive module: a porous and biodegradable component undertaking biological necessities of the scaffold. The load-bearing module is placed into the bio-reactive module to reinforce it. This paper is dedicated to optimizing the load-bearing module for a certain customized alveolar bone defect. More specifically, a 3D-printed skeleton, made of polycaprolactone (PCL), is optimized based on the boundary conditions of the …

The Behavior Of Partially Coherent Twisted Space-Time Beams In Atmospheric Turbulence, Milo W. Hyde Iv

Faculty Publications

We study how atmospheric turbulence affects twisted space-time beams, which are non-stationary random optical fields whose space and time dimensions are coupled with a stochastic twist. Applying the extended Huygens–Fresnel principle, we derive the mutual coherence function of a twisted space-time beam after propagating a distance z through atmospheric turbulence of arbitrary strength. We specialize the result to derive the ensemble-averaged irradiance and discuss how turbulence affects the beam’s spatial size, pulse width, and space-time twist. Lastly, we generate, in simulation, twisted space-time beam field realizations and propagate them through atmospheric phase screens to validate our analysis.

Radiogenomics Of C9orf72 Expansion Carriers Reveals Global Transposable Element Derepression And Enables Prediction Of Thalamic Atrophy And Clinical Impairment, Luke W. Bonham, Ethan G. Geier, Daniel W. Sirkis, Josiah K. Leong, Eliana Marisa Ramos, Qing Wang, Anna Karydas, Suzee E. Lee, Virginia E. Sturm, Russell P. Sawyer, Adit Friedberg, Justin K. Ichida, Aaron D. Gitler, Leo Sugrue, Michael Cordingley, Walter Bee, Eckard Weber, Joel H. Kramer, Katherine P. Rankin, Howard J. Rosen, Adam L. Boxer, William W. Seeley, John Ravits, Bruce L. Miller, Jennifer S. Yokoyama

Psychological Science Faculty Publications and Presentations

Hexanucleotide repeat expansion (HRE) within C9orf72 is the most common genetic cause of frontotemporal dementia (FTD). Thalamic atrophy occurs in both sporadic and familial FTD but is thought to distinctly affect HRE carriers. Separately, emerging evidence suggests widespread derepression of transposable elements (TEs) in the brain in several neurodegenerative diseases, including C9orf72 HRE-mediated FTD (C9-FTD). Whether TE activation can be measured in peripheral blood and how the reduction in peripheral C9orf72 expression observed in HRE carriers relates to atrophy and clinical impairment remain unknown. We used FreeSurfer software to assess the effects of C9orf72 HRE and clinical diagnosis (n …